We have shown that over-the-counter doses of the common analgesics ibuprofen and acetaminophen block the normal increase in skeletal muscle protein synthesis following resistance exercise. These two drugs are the most commonly used drugs by individuals that suffer from osteoarthritis, who number nearly 25 million in the United States. Many of these individuals are over the age of 65 y and are increasing their physical activity through resistance exercise as a result of a physician recommendation to help their arthritis or to improve their muscle strength, functional status, and overall health. Chronic consumption of acetaminophen or ibuprofen, or similar analgesic and anti-inflammatory drugs, may chronically inhibit skeletal muscle protein synthesis and the resultant hypertrophy and strength gains in strength training individuals. We propose to study two groups of older (65-80 y) women and men who have arthritis: 1) Those that have upper-body osteoarthritis (i.e., of the hand or shoulder), and 2) Those that have lower-body osteoarthritis (i.e., of the knee). This grouping will allow us to study individuals that need to take analgesic therapy and to separate the effects of the drugs on the exercise responses from the ability to perform the exercise, which may or may not be compromised in those individuals with osteoarthritis of the knee. We will examine the fractional rate of muscle protein synthesis (FSR), muscle hypertrophy (size) using magnetic resonance imaging and muscle fiber size, and muscle strength before and after four months of resistance exercise training of the lower body in an age-matched group that does not take any drug (control group), and upper- and lower-body arthritic groups that consume either acetaminophen (4 g.d-1) or ibuprofen (1.2 g.d-1) during the training period. We hypothesize that skeletal muscle FSR, size, and strength will be increased in the control group, while increases in these variables will be blunted in both the upper-body and lower-body arthritic groups that consume acetaminophen or ibuprofen. Dr. Trappe, a new investigator, and the co-investigators in the Department of Geriatrics and the Division of Rheumatology at UAMS have experience in all of the proposed methodologies. This investigation will provide important information for clinicians and older individuals with regard to expected benefits from physical activity during periods of analgesic and anti-inflammatory based therapy.